Shi Chuanqin, Xu Xue, Yu Xiaofeng, Du Zhenzhen, Luan Xiying, Liu Dachang, Hu Tao
Department of Immunology, Binzhou Medical University, Yantai, PR China.
Department of Clinical Microbiology, Linzi District People's Hospital, Linzi, PR China.
Mol Immunol. 2017 Oct;90:98-105. doi: 10.1016/j.molimm.2017.06.250. Epub 2017 Jul 11.
Glycosylation is an important protein post-translational modification. In this process, the intermediate product, Tn antigen, arises from somatic mutations in core1β3-galactosyltransferase-specific molecular chaperone (Cosmc), which is required for the formation of active core1β3-galactosyltransferase (T-synthase). As a type of tumor-associated carbohydrate antigen, Tn antigen is mainly expressed in many human tumor cells and is absent in normal cells. Surprisingly, it is also expressed in normal activated T cells after in vitro stimulation, but the mechanism underlying its expression remains unclear. This study demonstrated that Tn antigen was expressed in activated T cells and that the percentage of positive (Tn) cells increased and subsequently decreased within 72h after stimulation with CD3/CD28 Dynabeads, with peak expression occurring at 48h. During activation, interleukin-4 (IL-4) expression in the T-cell supernatant consistently increased with Tn cells, and was inversely correlated with serum interferon gamma (IFN-γ) levels. Compared with unactivated (without CD3/CD28 Dynabead stimulation) T cells, the level of T-synthase transcription in activated T cells did not significantly change, whereas T-synthase activity and Cosmc transcription significantly decreased, accompanied by a further increase in methylation of the Cosmc promoter. The results also showed that Cosmc transcription and translation decreased and then increased, and that Cosmc promoter methylation was a dynamic process during T cell activation. These data suggest that hypermethylation of the Cosmc promoter may induce the expression of Tn antigen in activated T cells.
糖基化是一种重要的蛋白质翻译后修饰。在此过程中，中间产物Tn抗原源于核心1β3 - 半乳糖基转移酶特异性分子伴侣（Cosmc）的体细胞突变，而Cosmc是活性核心1β3 - 半乳糖基转移酶（T合酶）形成所必需的。作为一种肿瘤相关碳水化合物抗原，Tn抗原主要在许多人类肿瘤细胞中表达，正常细胞中不存在。令人惊讶的是，体外刺激后正常活化的T细胞中也有表达，但其表达的潜在机制仍不清楚。本研究表明，Tn抗原在活化的T细胞中表达，在用CD3/CD28 Dynabeads刺激后72小时内，阳性（Tn）细胞百分比先升高后降低，在48小时达到表达峰值。在活化过程中，T细胞上清液中的白细胞介素 - 4（IL - 4）表达随Tn细胞持续增加，且与血清干扰素γ（IFN - γ）水平呈负相关。与未活化（无CD3/CD28 Dynabead刺激）的T细胞相比，活化T细胞中T合酶转录水平无显著变化，而T合酶活性和Cosmc转录显著降低，同时Cosmc启动子甲基化进一步增加。结果还表明，Cosmc转录和翻译先降低后增加，且Cosmc启动子甲基化在T细胞活化过程中是一个动态过程。这些数据表明，Cosmc启动子的高甲基化可能诱导活化T细胞中Tn抗原的表达。
